This proposal is concerned with the total synthesis of compactin, a potent competitive inhibitor of HMG-CoA reductase using a combination of chemical and microbiological methods. Optically-active bifunctional C4, C5, C6, and C7 intermediates, which are important building blocks for the synthesis of macrolides possessing chiral methyl groups will be prepared by microbial hydrolysis of substrates possessing enantiotopic ester groupings.